The objectives of the proposed studies are to gain a more complete understanding of how Na+ excretion and conservation are regulated in the intact kidney and how the metabolism of substrates are linked to these regulatory mechanisms in normal and diseased kidneys. In particular we wish to determine whether the metabolism of glucose selectively provides the energy for support of Na+ reabsorption along the distal portion of the nephron. Since, in this region of the nephron hormones such as insulin, anti-diuretic hormone, aldosterone and norepinephrine as well as the "cardiac atrial natriuretic factor" manifest their action, we also will determine whether, when these mediators are present, there are simultaneous changes in the metabolism of glucose and in Na+ excretion. In order to define the metabolic and hormonal mechanisms which are linked to regulation of Na+ reabsorption we will do these studies with the isolated perfused rat kidney. In this preparation no neural or hormonal phenomena and the influence of other organs on renal function and metabolism are virtually absent. Therefore we can introduce each of these variables in controlled fashion. Similarly we can regulate the availability of glucose or other substrates to the kidney so that the discrete role of a substrate in permitting regulation of Na+ conservation can be determined. Thus from the simultaneous measurements of function and metabolism in kidneys from normal or from diseased (e.g. diabetes) animals we will be able to gain a more complete understanding of regulation of Na+ conservation.